Abstract:
:It is not clear whether TNF-α antagonists used in the treatment of psoriasis need to act systemically, or whether local inhibition of skin-produced TNF-α would be sufficient to silence skin inflammation. To answer this question, we conducted two multicentre, double-blinded, randomized, placebo-controlled clinical trials with the novel single-chain anti-TNF-α-PENTRA(®) -antibody DLX105. Upon intra-dermal injection, DLX105 induced a mean local PASI decrease of 33% over baseline after 2 weeks of treatment, while the placebo response was only 12% (P = 0.001). The clinical response was accompanied by changes in biomarkers such as reductions in K16, Ki67 and epidermal thickness as well as decreased mRNA levels of IL-17, TNF-α, IL-23p19, IL-12p40 and IFN-γ. Next, we applied the drug topically twice daily in a 0.5% hydrogel formulation. While the local PASI did not change, topical DLX105 mediated significant reductions of mRNA levels of key proinflammatory cytokines when compared to placebo, and this effect was further enhanced after weekly tape stripping of plaques to increase drug penetration. These results suggest that longer treatment periods and/or increased local drug concentrations might result in better therapeutic efficacy of topically applied DLX105. In sum, we can show for the first time that local inhibition of TNF-α is sufficient to mediate a biological response in psoriasis that translates into clinical efficacy.
journal_name
Exp Dermatoljournal_title
Experimental dermatologyauthors
Tsianakas A,Brunner PM,Ghoreschi K,Berger C,Loser K,Röcken M,Stingl G,Luger T,Jung Tdoi
10.1111/exd.12927subject
Has Abstractpub_date
2016-06-01 00:00:00pages
428-33issue
6eissn
0906-6705issn
1600-0625journal_volume
25pub_type
杂志文章,多中心研究,随机对照试验abstract::During aging, increases in the number of senescent cells are seen in various tissues. On the other hand, stem cells play crucial roles in tissue repair and homeostasis. Therefore, it is likely that stem cells give rise to new cells that replace senescent cells. However, how stem cells contribute to homeostasis in the ...
journal_title:Experimental dermatology
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journal_title:Experimental dermatology
pub_type: 杂志文章,随机对照试验
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journal_title:Experimental dermatology
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journal_title:Experimental dermatology
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